Transmitter release by non‐receptor activation of the α‐subunit of guanine nucleotide regulatory protein in rat striatal slices

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Abstract
The effects of 5 mM NaF + 10 μM AIC13, a direct activator of guanine nucleotide‐binding proteins (G proteins), on the release of [3H]dopamine ([3H]DA), [3H]gamma‐aminobutyric acid ([3H]GABA), and [3H]acethylcholine ([3H]ACh) were investigated in slices of rat striatum. When the tissue was exposed to NaF + AIC13 the release of [3H]DA, [3H]GABA, and [3H]ACh was enhanced significantly. In a calcium free solution the release of [3H]GABA and [3H]DA was increased by NaF + A1C13 much more than in the presence of [Ca2+]. In slice preparations taken from reserpinized animals, in which the vesicular storage of [3H]DA was therefore prevented, NaF + AIC13 had no effect on [3H]DA release. HPLC analysis of the radioactivity of the perfusate showed that, in the presence of NaF + AICI3, the content of dihydroxyphenylacetic acid (DOPAC) in perfusate samples increased significantly, while in pargyliue‐treated animals only the DA content was increased. Inhibition of DA carriers by nomifensine or low temperature prevented the effect of NaF + AIC13. N‐ethylmaleimide (NEM) preincubation did not modify the effect of NaF + AICl3 on [3H]DA release. Neomycin (0.1 mM), a phospholipase C (PLC) inhibitor, significantly decreased the effect of NaF + AlC13 on [3H]DA and [3H]GABA release. The internal concentration of Ca2+ in synaptosomes was enhanced by NaF + AIC13 in normal solution. However, [Ca2+]i was not influenced by NaF + AIC13 in Ca2+ ‐free medium. It is concluded that a non‐receptor‐mediated activation, by NaF + AICl3, of the a‐subunit of a G protein, results in a [Ca2+]o,‐independent release of DA and GABA, but not that of ACh.